80 results match your criteria fusion fzo1


dnm1 deletion blocks mitochondrial fragmentation in Δfzo1 cells.

Yeast 2021 03 4;38(3):197-205. Epub 2021 Feb 4.

Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, 1 Wen Yuan Rd., Nanjing, 210023, China.

Mitochondrial division and fusion play critical roles in maintaining functional mitochondria. Fzo1 is an outer mitochondrial membrane GTPase that played an essential role in mitochondrial fusion in budding yeast Saccharomyces cerevisiae. Here, we report the characterization of the Schizosaccharomyces pombe homologue of S. Read More

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Loss of FZO1 gene results in changes of cell dynamics in fission yeast.

Int J Mol Med 2020 Dec 12;46(6):2194-2206. Epub 2020 Oct 12.

Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), College of Life Sciences, China West Normal University, Nanchong, Sichuan 637009, P.R. China.

Mitochondrial fission and fusion dynamics are critical cellular processes, and abnormalities in these processes are associated with severe human disorders, such as Beckwith‑Wiedemann syndrome, neurodegenerative diseases, Charcot‑Marie‑Tooth disease type 6, multiple symmetric lipomatosis and microcephaly. Fuzzy onions protein 1 (Fzo1p) regulates mitochondrial outer membrane fusion. In the present study, Schizosaccharomyces pombe (S. Read More

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December 2020

Mitochondrial Fusion: The Machineries In and Out.

Authors:
Song Gao Junjie Hu

Trends Cell Biol 2021 01 19;31(1):62-74. Epub 2020 Oct 19.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion. Disruption of mitochondrial dynamics undermines their function and causes several human diseases. The fusion of the outer (OMM) and inner mitochondrial membranes (IMM) is mediated by two classes of dynamin-like protein (DLP): mitofusin (MFN)/fuzzy onions 1 (Fzo1) and optic atrophy 1/mitochondria genome maintenance 1 (OPA1/Mgm1). Read More

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January 2021

Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion.

Int J Mol Sci 2020 Sep 18;21(18). Epub 2020 Sep 18.

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Straße 26, 50931 Cologne, Germany.

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. Read More

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September 2020

The regulation of mitochondrial homeostasis by the ubiquitin proteasome system.

Biochim Biophys Acta Bioenerg 2020 12 27;1861(12):148302. Epub 2020 Aug 27.

Sorbonne Université, CNRS, UMR8226, Institut de Biologie Physico-Chimique, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, F-75005 Paris, France. Electronic address:

From mitochondrial quality control pathways to the regulation of specific functions, the Ubiquitin Proteasome System (UPS) could be compared to a Swiss knife without which mitochondria could not maintain its integrity in the cell. Here, we review the mechanisms that the UPS employs to regulate mitochondrial function and efficiency. For this purpose, we depict how Ubiquitin and the Proteasome participate in diverse quality control pathways that safeguard entry into the mitochondrial compartment. Read More

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December 2020

Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation.

Life Sci Alliance 2020 01 19;3(1). Epub 2019 Dec 19.

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

Mitochondria are essential organelles whose function is upheld by their dynamic nature. This plasticity is mediated by large dynamin-related GTPases, called mitofusins in the case of fusion between two mitochondrial outer membranes. Fusion requires ubiquitylation, attached to K398 in the yeast mitofusin Fzo1, occurring in atypical and conserved forms. Read More

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January 2020

A AAA ATPase Cdc48 with a cofactor Ubx2 facilitates ubiquitylation of a mitochondrial fusion-promoting factor Fzo1 for proteasomal degradation.

J Biochem 2020 Mar;167(3):279-286

Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.

Dynamic functionality of mitochondria is maintained by continual fusion and fission events. A mitochondrial outer membrane protein Fzo1 plays a pivotal role upon mitochondrial fusion by homo-oligomerization to tether fusing mitochondria. Fzo1 is tightly regulated by ubiquitylations and the ubiquitin-responsible AAA protein Cdc48. Read More

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Plasticity in salt bridge allows fusion-competent ubiquitylation of mitofusins and Cdc48 recognition.

Life Sci Alliance 2019 12 18;2(6). Epub 2019 Nov 18.

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany

Mitofusins are dynamin-related GTPases that drive mitochondrial fusion by sequential events of oligomerization and GTP hydrolysis, followed by their ubiquitylation. Here, we show that fusion requires a trilateral salt bridge at a hinge point of the yeast mitofusin Fzo1, alternatingly forming before and after GTP hydrolysis. Mutations causative of Charcot-Marie-Tooth disease massively map to this hinge point site, underlining the disease relevance of the trilateral salt bridge. Read More

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December 2019

Structural dataset from microsecond-long simulations of yeast mitofusin Fzo1 in the context of membrane docking.

Data Brief 2019 Oct 31;26:104460. Epub 2019 Aug 31.

Institut de Biologie Physico-Chimique-Fondation Edmond de Rothschild, PSL Research University, Paris, France.

In this work we present a novel set of possible auto-oligomerisation states of yeast protein Fzo1 in the context of membrane docking. The dataset reports atomistic models and trajectories derived from a molecular dynamics study of the yeast mitofusin Fzo1, residues 101-855. The initial modelling was followed by coarse-grained molecular dynamics simulation to evaluate the stability and the dynamics of each structural model in a solvated membrane environment. Read More

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October 2019

A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin.

J Membr Biol 2019 10 4;252(4-5):293-306. Epub 2019 Sep 4.

CNRS, Université de Paris, UPR 9080, Laboratoire de Biochimie Théorique, 13 Rue Pierre et Marie Curie, 75005, Paris, France.

Mitochondria are dynamic organelles characterized by an ultrastructural organization which is essential in maintaining their quality control and ensuring functional efficiency. The complex mitochondrial network is the result of the two ongoing forces of fusion and fission of inner and outer membranes. Understanding the functional details of mitochondrial dynamics is physiologically relevant as perturbations of this delicate equilibrium have critical consequences and involved in several neurological disorders. Read More

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October 2019

Physics-based oligomeric models of the yeast mitofusin Fzo1 at the molecular scale in the context of membrane docking.

Mitochondrion 2019 11 12;49:234-244. Epub 2019 Jul 12.

CNRS, Université de Paris, UPR 9080, Laboratoire de Biochimie Théorique, UPR 9080, 13 rue Pierre et Marie Curie, F-75005, Paris, France; Institut de Biologie Physico-Chimique-Fondation Edmond de Rothschild, PSL Research University, Paris, France. Electronic address:

Tethering and homotypic fusion of mitochondrial outer membranes is mediated by large GTPases of the dynamin-related proteins family called the mitofusins. The yeast mitofusin Fzo1 forms high molecular weight complexes and its assembly during membrane fusion likely involves the formation of high order complexes. Consistent with this possibility, mitofusins form oligomers in both cis (on the same lipid bilayer) and trans to mediate membrane attachment and fusion. Read More

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November 2019

Mitochondrial dynamics and mitophagy are necessary for proper invasive growth in rice blast.

Mol Plant Pathol 2019 08 20;20(8):1147-1162. Epub 2019 Jun 20.

Temasek Life Sciences Laboratory, and Department of Biological Sciences, 1 Research Link, National University of Singapore, 117604, Singapore.

Magnaporthe oryzae causes blast disease, which is one of the most devastating infections in rice and several important cereal crops. Magnaporthe oryzae needs to coordinate gene regulation, morphological changes, nutrient acquisition and host evasion in order to invade and proliferate within the plant tissues. Thus far, the molecular mechanisms underlying the regulation of invasive growth in planta have remained largely unknown. Read More

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Mitofusins: Disease Gatekeepers and Hubs in Mitochondrial Quality Control by E3 Ligases.

Front Physiol 2019 9;10:517. Epub 2019 May 9.

Center for Molecular Medicine Cologne (CMMC), Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Mitochondria are dynamic organelles engaged in quality control and aging processes. They constantly undergo fusion, fission, transport, and anchoring events, which empower mitochondria with a very interactive behavior. The membrane remodeling processes needed for fusion require conserved proteins named mitofusins, MFN1 and MFN2 in mammals and Fzo1 in yeast. Read More

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Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress.

Mol Biol Cell 2019 08 29;30(17):2141-2154. Epub 2019 May 29.

Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.

Mitochondrial decline is a hallmark of aging, and cells are equipped with many systems to regulate mitochondrial structure and function in response to stress and metabolic alterations. Here, using budding yeast, we identify a proteolytic pathway that contributes to alterations in mitochondrial structure in aged cells through control of the mitochondrial fusion GTPase Fzo1. We show that mitochondrial fragmentation in old cells correlates with reduced abundance of Fzo1, which is triggered by functional alterations in the vacuole, a known early event in aging. Read More

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Maintenance of Mitochondrial Morphology in Cryptococcus neoformans Is Critical for Stress Resistance and Virulence.

mBio 2018 11 6;9(6). Epub 2018 Nov 6.

Department of Molecular Microbiology, Washington University School of Medicine, Washington University, St. Louis, Missouri, USA

Mitochondria are essential organelles that act in pathways including ATP production, β-oxidation, and clearance of reactive oxygen species. They occur as a complex reticular network that constantly undergoes fusion and fission, mediated by dynamin-related proteins (DRPs). DRPs include Fzo1, which mediates fusion, and Dnm1, Mdv1, and Fis1, which mediate fission. Read More

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November 2018

Dual roles of mitochondrial fusion gene FZO1 in yeast age asymmetry and in longevity mediated by a novel ATG32-dependent retrograde response.

Biogerontology 2019 02 8;20(1):93-107. Epub 2018 Oct 8.

Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave., MBC 8513, New Orleans, LA, 70112, USA.

The replicative lifespan of the yeast Saccharomyces cerevisiae models the aging of stem cells. Age asymmetry between the mother and daughter cells is established during each cell division, such that the daughter retains the capacity for self-renewal while this ability is diminished in the mother. The segregation of fully-functional mitochondria to daughter cells is one mechanism that underlies this age asymmetry. Read More

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February 2019

Two Cdc48 cofactors Ubp3 and Ubx2 regulate mitochondrial morphology and protein turnover.

J Biochem 2018 Nov;164(5):349-358

Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, Japan.

Mitochondria continuously undergo coordinated fusion and fission during vegetative growth to keep their homogeneity and to remove damaged components. A cytosolic AAA ATPase, Cdc48, is implicated in the mitochondrial fusion event and turnover of a fusion-responsible GTPase in the mitochondrial outer membrane, Fzo1, suggesting a possible linkage of mitochondrial fusion and Fzo1 turnover. Here, we identified two Cdc48 cofactor proteins, Ubp3 and Ubx2, involving mitochondria regulation. Read More

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November 2018

Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion.

Elife 2018 01 8;7. Epub 2018 Jan 8.

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.

Cdc48/p97, a ubiquitin-selective chaperone, orchestrates the function of E3 ligases and deubiquitylases (DUBs). Here, we identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. The DUBs Ubp12 and Ubp2 exert opposing effects on mitochondrial fusion and cleave different ubiquitin chains on the mitofusin Fzo1. Read More

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January 2018

A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space.

J Cell Biol 2018 02 6;217(2):507-515. Epub 2017 Dec 6.

Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Read More

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February 2018

A membrane-inserted structural model of the yeast mitofusin Fzo1.

Sci Rep 2017 08 31;7(1):10217. Epub 2017 Aug 31.

Institut de Biologie Physico-Chimique, Laboratoire de Biochimie Théorique, UPR 9080, Centre National de la Recherche Scientifique, Paris, France.

Mitofusins are large transmembrane GTPases of the dynamin-related protein family, and are required for the tethering and fusion of mitochondrial outer membranes. Their full-length structures remain unknown, which is a limiting factor in the study of outer membrane fusion. We investigated the structure and dynamics of the yeast mitofusin Fzo1 through a hybrid computational and experimental approach, combining molecular modelling and all-atom molecular dynamics simulations in a lipid bilayer with site-directed mutagenesis and in vivo functional assays. Read More

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An ubiquitin-dependent balance between mitofusin turnover and fatty acids desaturation regulates mitochondrial fusion.

Nat Commun 2017 06 13;8:15832. Epub 2017 Jun 13.

Sorbonne Universités, UPMC University of Paris 06, CNRS, UMR8226, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, 75005 Paris, France.

Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Read More

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A Role of the FUZZY ONIONS LIKE Gene in Regulating Cell Death and Defense in Arabidopsis.

Sci Rep 2016 11 29;6:37797. Epub 2016 Nov 29.

Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Programmed cell death (PCD) is critical for development and responses to environmental stimuli in many organisms. FUZZY ONIONS (FZO) proteins in yeast, flies, and mammals are known to affect mitochondrial fusion and function. Arabidopsis FZO-LIKE (FZL) was shown as a chloroplast protein that regulates chloroplast morphology and cell death. Read More

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November 2016

Regulation of Mitofusin1 by Mahogunin Ring Finger-1 and the proteasome modulates mitochondrial fusion.

Biochim Biophys Acta 2016 12 4;1863(12):3065-3083. Epub 2016 Oct 4.

Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, 700064, India. Electronic address:

Health and homoeostasis are maintained by a dynamic balance between mitochondrial fission and fusion. Mitochondrial fusion machinery is largely unknown in mammals. Only a few reports have illustrated the role of Fzo1 in mitochondrial fusion known in Saccharomyces cerevisiae. Read More

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December 2016

Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae.

Mol Biol Cell 2016 Mar 13;27(5):776-87. Epub 2016 Jan 13.

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032

Higher-functioning mitochondria that are more reduced and have less ROS are anchored in the yeast bud tip by the Dsl1-family protein Mmr1p. Here we report a role for mitochondrial fusion in bud-tip anchorage of mitochondria. Fluorescence loss in photobleaching (FLIP) and network analysis experiments revealed that mitochondria in large buds are a continuous reticulum that is physically distinct from mitochondria in mother cells. Read More

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Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion.

Mol Cell Biol 2016 01 9;36(2):347-62. Epub 2015 Nov 9.

Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

Mitochondria are vital and highly dynamic organelles that continuously fuse and divide to maintain mitochondrial quality. Mitochondrial dysfunction impairs cellular integrity and is known to be associated with various human diseases. However, the mechanism by which the quality of mitochondria is maintained remains largely unexplored. Read More

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January 2016

MitoLoc: A method for the simultaneous quantification of mitochondrial network morphology and membrane potential in single cells.

Mitochondrion 2015 Sep 13;24:77-86. Epub 2015 Jul 13.

Dept. of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, UK; The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.

Mitochondria assemble into flexible networks. Here we present a simple method for the simultaneous quantification of mitochondrial membrane potential and network morphology that is based on computational co-localisation analysis of differentially imported fluorescent marker proteins. Established in, but not restricted to, Saccharomyces cerevisiae, MitoLoc reproducibly measures changes in membrane potential induced by the uncoupling agent CCCP, by oxidative stress, in respiratory deficient cells, and in ∆fzo1, ∆ref2, and ∆dnm1 mutants that possess fission and fusion defects. Read More

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September 2015

Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder.

Nat Genet 2015 Aug 13;47(8):926-32. Epub 2015 Jul 13.

Department of Pediatrics, Division of Medical Genetics, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Dominant optic atrophy (DOA) and axonal peripheral neuropathy (Charcot-Marie-Tooth type 2, or CMT2) are hereditary neurodegenerative disorders most commonly caused by mutations in the canonical mitochondrial fusion genes OPA1 and MFN2, respectively. In yeast, homologs of OPA1 (Mgm1) and MFN2 (Fzo1) work in concert with Ugo1, for which no human equivalent has been identified thus far. By whole-exome sequencing of patients with optic atrophy and CMT2, we identified four families with recessive mutations in SLC25A46. Read More

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Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion.

Proc Natl Acad Sci U S A 2015 Mar 17;112(9):E947-56. Epub 2015 Feb 17.

Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, and

Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. Read More

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Biosynthesis and roles of phospholipids in mitochondrial fusion, division and mitophagy.

Cell Mol Life Sci 2014 Oct 28;71(19):3767-78. Epub 2014 May 28.

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Mitochondria move, fuse and divide in cells. The dynamic behavior of mitochondria is central to the control of their structure and function. Three conserved mitochondrial dynamin-related GTPases (i. Read More

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October 2014

Activation of the pleiotropic drug resistance pathway can promote mitochondrial DNA retention by fusion-defective mitochondria in Saccharomyces cerevisiae.

G3 (Bethesda) 2014 May 7;4(7):1247-58. Epub 2014 May 7.

Department of Molecular Biology and Genetic, Koç University, Sarıyer, İstanbul, 34450, Turkey

Genetic and microscopic approaches using Saccharomyces cerevisiae have identified many proteins that play a role in mitochondrial dynamics, but it is possible that other proteins and pathways that play a role in mitochondrial division and fusion remain to be discovered. Mutants lacking mitochondrial fusion are characterized by rapid loss of mitochondrial DNA. We took advantage of a petite-negative mutant that is unable to survive mitochondrial DNA loss to select for mutations that allow cells with fusion-deficient mitochondria to maintain the mitochondrial genome on fermentable medium. Read More

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